Heart failure is the leading cause of death in the United States. The availability of an effective, reliable mechanical replacement for the failing human heart would have an enormous impact on health care. Nevertheless, the technical challenges inherent in developing a total artificial heart (TAH) have, to date, proven prohibitive. Recently, continuous-flow (CF) blood pumps have been introduced into clinical medicine as ventricular assist devices. These pumps are smaller, simpler, and more robust than their pulsatile predecessors. In addition, CF-pumps have the intrinsic ability to adjust pump output based on inflow and outflow pressure. Researchers at the Texas Heart Institute (THI) are capitalizing on these advantages by developing a novel continuous-flow total artificial heart (CF-TAH) comprising two modified CF-pumps used in series: one dedicated to the systemic and the other to the pulmonary circulation. The inflow sensitivity of CF- pumps makes them uniquely suited for integration into a TAH as they have the potential to autonomously balance systemic and pulmonary flow. Preliminary animal studies at THI using dual CF-pumps for total heart replacement have demonstrated feasibility, with up to 7 weeks of survival and normal physiologic function. The specific aims of this program are (1) to develop a CF-TAH that allow patients with advanced heart failure to regain meaningful and acceptable quality of life, and (2) to develop a control system for operation of the CF- TAH that responds to changing demands. To achieve these aims, the PI, O. H. Frazier (THI), will lead a collaborative group of four institutions in the Texas Medical Center (THI, MicroMed Cardiovascular, Inc., University of Houston, and Rice University). Computer modeling and in vitro and in vivo experiments will be used to modify current CF-pump technology, integrate two CF-pumps into a CF-TAH design, and develop the control system and patient-pump interface. The assembled team has extensive experience in medical device development, mechanical engineering, materials science, bioengineering, computational modeling, animal research, and cardiac surgery. On the basis of their successful history of research collaboration, geographic proximity, and wealth and breadth of experience and expertise, this multi-institutional group is uniquely suited for the challenging but important task of developing an effective, reliable, and economical TAH. PUBLIC HEALTH RELEVANCE Heart failure is the leading cause of death in the United States. The goal of this project is to develop a new total artificial heart (TAH) using two continuous-flow blood pumps. These pumps are smaller than the older, pulsatile pumps and can therefore be implanted in children and smaller adults. The continuous-flow TAH would also be simpler to control and would have excellent reliability. The availability of an effective, reliable replacement such as the continuous-flow TAH for the failing human heart would thus have an enormous impact on health care.